For the last 40-50 years it has been known that testicular descent is controlled by male androgenic hormones (testosterone). Androgens were proposed to act directly or indirectly on mesenchymal tissue in the groin known as the gubernaculum, which migrates across the pubic region from the groin to the scrotum during inguino-scrotal testicular descent. The gubernaculum was thought to guide the testes into the scrotum.
In humans, approximately 5% of male babies are born with undescended testes. In 1-2% of males the testes remain undescended while the remainder descend in the first few months. Normally, the testes are fully descended by 30-36 weeks gestation. Testes descending postnatally are not quite normal and many re-ascend out of the scrotum later in childhood.
The treatment for undescended testes is either invasive surgery (orchidopexy), where the undescended organ is physically transferred to the scrotum, or hormonal therapy, which in a small number of children may stimulate descent without operation.
One of the main complications of undescended testes, and a primary reason for surgical intervention, is the risk of subsequent infertility. Many boys, however, have undergone successful repositioning of the testis in the scrotum but have suffered persisting infertility which has not been corrected by surgery.
Chivers et al. (J. Ped. Surg. 21, 691, 1986) have described the frequency of azospermia (no sperm production) or oligospermia (insufficient sperm production) in males suffering from one (unilateral) or two (bilateral) undescended testicles, either without treatment, after surgical repositioning of the testes (orchidopexy), or offer both orchidopexy and hormone treatment with HCG (human chorionic gonadotrophin). The results obtained by Chivers et al. are as follows:
______________________________________ Frequency of Azospermia Bilateral Unilaterial ______________________________________ No treatment 100% 44% Orchidopexy 74% 41% HCG and orchidopexy 73% 49% ______________________________________
It is clear from the results that sperm production is quite low even after orchidopexy, and that hormone treatment has little effect.
The function of the testis is very dependent on its temperature, with the best function at 33.degree. C., this being 4.degree. C. below normal internal body temperature. The reason that the testis normally resides in the scrotum is to provide a low-temperature environment which provides the maximum viability of spermatozoa stored in the adjacent epididymis.
Where the testis remains out of the scrotum during childhood, progressive changes of degeneration are observed. The germ cells of the testis progressively disappear between 6 months and 2 years, while the interstitial tissue between the seminiferous tubules becomes thicker. The tubules themselves eventually become small and atrophic.
The germ cells are present in large numbers in the tubules at birth, and they have the appearance of primitive germ cells. Between about 4 months and 2 years these germ cells undergo a crucial series of developmental steps or "transformations", so that they end up with the appearance of "primary spermatocytes". The sequence of cell types involved in the transformation is: ##STR1##
During this transformation phase the total number of germ cells falls even in normal testes, but then the primary spermatocytes "repopulate" the tubules. The transformation phase does not occur normally in undescended testes and this is believed to account for the subsequent infertility (Huff et al., 1989, J. Immonol. 142: 506-508).
Some advocates of hormonal therapy, which has now been shown to be successful in only a small percentage of boys (Rajfer et al, 1986, N. Eng. J. Med., 314: 466-470; De Munick Keizer-Schrama et al, 1986, Lancet 11: 876-879), have suggested that gonadotrophin hormones might still have a role in stimulating germ cell development after surgical intervention. The mechanism by which gonadotrophins may act is not known.